[Modulation of peritoneal macrophage function: effect of selected drugs on their activity and sperm phagocytosis].
Leukocytes and their products (free oxygen radicals, cytokines, nitrogen intermediates and prostanoids) are considered to be the major etiopathological factors of male and female infertility. Particular attention is paid to macrophages, which play a crucial role in pathogenesis of infertility. They may modulate immunological response which is often directed towards spermatozoa, decreasing their ability to move, and fertilize egg cells. Spermatozoa are often phagocytosed by the macrophages. The immune cells may also damage egg cells and embryos, or even impair implantation. The aim of the work was to verify the influence of potentially immunomodulating drugs: nifedipine, danazol and acetylsalicylic acid on the activity of peritoneal macrophages. Mouse peritoneal macrophages were cultured with the studied drugs and spermatozoa. It was assumed that the production and release of tumor necrosis factor-alpha, nitrates and prostaglandin F2 alpha were indicative of the increased activity of the macrophages. Biochemical studies were correlated with the morphological ones conducted under transmission and scanning electron microscopes. These studies covered the morphology of the cells as well as the sperm phagocytosis by the macrophages. Nifedipine was found to decrease the release of nitrites and TNF alpha by the peritoneal macrophages (Tab. 1, 4, 5). The inhibitory effect was dose and time dependent. Nifedipine caused morphological changes which correlated with the decreased activity of the cells (Fig. 3, 4). The macrophages were round with short protrusions surrounding the spermatozoa. There were numerous endocytic vesicles in the cytoplasm of the macrophages. Danazol did not exert any effect on the activity of the studied peritoneal macrophages (Tab. 2, 4, 5). At higher concentration, a decreased release of nitrites and TNF alpha was noted. This correlated with necrotic changes in the scanning and transmission electron microscopes (Fig. 5, 6). The changes were seen in the studied macrophages and spermatozoa. The sperm phagocytosis was completely abolished. The acetylsalicylic acid had an inhibitory effect on the release of nitrites, PGF2 alpha and TNF alpha (Tab. 3, 4, 5). The effect was dose, and time dependent. It was not noted in the concentration lower than therapeutical. Acetylsalicylic acid did not cause any morphological changes, but the phagocytosis was inhibited (Fig. 7, 8). The experiments were to verify new potential possibilities of infertility treatment, particularly those depending on the malfunction of the immunological system.
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Z Katedry i Zakładu Histologii i Embriologii Pomorskiej Akademii Medycznej w Szczecinie, Szczecin.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure; D003613:Danazol / Q000494:pharmacology*; D015237:Dinoprost / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008432:Mathematical Computing; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009543:Nifedipine / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D013094:Spermatozoa / Q000648:ultrastructure*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D015237:Dinoprost; D009543:Nifedipine; D003613:Danazol; D001241:Aspirin
Modulacja funkcji makrofagów otrzewnowych: wpływ wybranych leków na ich aktywność oraz fagocytoze plemników.